Concurrent EGFr and Cox-2 expression in colorectal cancer: proliferation impact and tumour spreading

Background: Many reports were produced on single epidermal growth factor receptor (EGFr) and cyclo-oxygenase-2 (Cox-2) evaluation using immunohistochemical techniques (IHC), but very few works considered concurrent expression of these two proteins in the light of their impact on proliferation and tumour spreading. At least three molecular pathways ( EGFr, Cox-2, and APC/beta-catenin molecular cascade) may interact in this malignancy giving rise to cross talking effects on proliferation and cancer spreading. Patients and methods: To better detail these two latter aggressive features, we studied 205 sporadic colorectal cancer patients, comparing concurrent expression of EGFr, Cox-2, Ki-67, Cyclins D1-A, and E, with tumour spreading ( budding) ( BUD) and pN status. Results: Our results point to a different aggressive molecular profile due to Cox-2 expression. Cox-2 High expressing cases showed a clear EGFr proliferation-promoting role. On the contrary, EGFr seems directly involved in cancer cells spreading rather than in promoting cancer proliferation in Cox-2 Low/Negative cases. Conclusions: Immunohistochemical profiling of colorectal cancer seems to be a promising approach, not only to define prognostic impact, but also to detail proliferation-related molecular interplays between EGFr and Cox-2 pathways, with these two latter proteins, at present, being the hottest pharmacological targets for colorectal cancer (CRC) chemoprevention and therapy.